The effects of (-)-daurisoline on Ca2+ influx in presynaptic nerve terminals.
1. The effects of (-)-daurisoline on 45Ca2+ uptake and [3H]-gamma-aminobutyric acid ([3H]-GABA) release from synaptosomes of rat cerebral cortex and on contractile activity of rat aorta were examined. 2. Application of (-)-daurisoline (1-100 microM) produced concentration-related inhibition of high K(+)-stimulated 45Ca2+ uptake and [3H]-GABA release (IC50 = 7.7 +/- 0.9 microM and 10.0 +/- 1.5 microM, respectively) in synaptosomes but verapamil was only weakly active. 3. Neither (-)-daurisoline (100 microM) nor verapamil (100 microM) modified 45Ca2+ uptake in control medium (5 mM K+, resting uptake) and [3H]-GABA release in Ca-free medium (45 mM K+ basal release). 4. High K+ and noradrenaline-evoked contractions of rat aorta were inhibited by both (-)-daurisoline and verapamil. 5. In conclusion, (-)-daurisoline, which differed from verapamil in its mode of blocking Ca2+ influx may be a potent Ca2+ antagonist of Ca2+ channels in neurones.
Lu
Y M
YM
Department of Pharmacology, China Pharmaceutical University, Nanjing.
Liu
G Q
GQ
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D005680:gamma-Aminobutyric Acid; C023968:daurisoline; D014700:Verapamil; D011188:Potassium; D009638:Norepinephrine